The ability to successfully form memories for arbitrary associations is essential for most acts of daily living. Numerous studies have shown that the hippocampus plays a critical role in associative memory. Recent work indicates that the perirhinal cortex (PRc) is also involved, but its functional role in associative memory is poorly understood. This research program will use functional magnetic resonance imaging (FMRI) and novel behavioral paradigms to test three theories of how the PRc contributes to associative recognition: (1) Unitization theory asserts that the PRc can support familiarity-based recognition of novel associations if the paired items are encoded as a single unit, but that the hippocampus is required for recollection of relations between items that are encoded as separate units. Novel FMRI experiments are proposed to test whether the PRc specifically contributes to recognition of associations between pairs of items that were encoded as a single unit. Parallel behavioral studies will test whether unitization influences indices of familiarity. (2) Domain theory asserts that the PRc supports familiarity-based recognition for associations between items from the same processing domain, but that the hippocampus is required to support recollection for associations between items from different processing domains. Novel FMRI studies are proposed to test whether the PRc supports associations between items from the same processing domains, but not associations between items from different domains. In addition, behavioral studies will test whether within-domain, but not across-domain associations influence the behavioral indices of familiarity. (3) Binding of items and contexts (BIC) theory asserts that the PRc represents item information, the PHc represents context information, and that this information is bound by the hippocampus. FMRI experiments are proposed to test whether recall of item information will be associated with PRc activity, whereas the recall of contextual information will lead to PHc activity. By testing the three theories, this proposal can provide the foundation for the development of a comprehensive theory of MTL function that can incorporate the influences of encoding processing, stimulus domain, and retrieval processing. Several psychiatric (e.g., schizophrenia) and neurological (e.g., Alzheimer's disease and traumatic brain injury) disorders are associated with memory impairments and with medial temporal lobe dysfunction. The proposed research may lead to improved diagnostic and therapeutic approaches to these disorders. PUBLIC HEALTH RELEVANCE Basic research on the mnemonic functions of the medial temporal lobe region is critically important because several psychiatric (e.g., schizophrenia) and neurological (e.g., Alzheimer's disease and traumatic brain injury) disorders are associated with memory impairments and MTL dysfunction. Such memory disorders can have a devastating effect on patients'quality of life. Research clarifying the basic neural mechanisms of memory can lead to improved diagnosis and treatment of these disorders.